This project studies the structure, function, and regulation of mammalian taste receptors and other molecules involved in taste signaling. In collaboration with Susan Sullivan in the NIDCD Division of Intramural Research, we have created a subtracted, normalized mouse cDNA library enriched in genes selectively expressed in taste receptor cells. From this library, we have isolated hundreds of cDNAs from taste receptor cell selective expression, when assayed by in situ hybridization. These cDNAs include members of the sweet and bitter taste receptor families, as well as G protein subunits, ion channels, and other molecules likely to be involved in taste signaling. We are currently using heterologous expression and mouse models to explore the function of these taste-selective molecules. In a collaboration with John Northup's laboratory in the NIDCD Division of Intramural Research, we are using an in vitro receptor reconstitution assay to study the ligand preferences and coupling properties of normal and mutated bitter receptors.